[LLY AHP WLA] Labels hide diet drug mixture risk - U.S. research
Friday August 28, 12:10 am Eastern Time
By Leslie Gevirtz
BOSTON, Aug 27 (Reuters) - Outdated labeling hides a popular
diet drug's dangerous side effects when combined with antidepressants such as Prozac or cold remedies like Sudafed, researchers said on Friday.
The diet drug phentermine -- the ''phen'' in the now banned combination fen-phen -- has been used in the United States since 1961 and remains on the market. It is widely prescribed to treat obesity, a
problem that afflicts some 65 million Americans.
But the U.S. Food and Drug Administration has never updated the drug's warning label to include crucial information, according to researchers at the Massachusetts Institute of Technology and the Massachusetts College of Pharmacy. Phentermine blocks the body's ability to remove serotonin from the blood stream.
Serotonin is involved in transmitting nerve impulses, and the antidepressant and anti-obesity drugs are designed to enhance that effect. But too much serotonin can damage blood vessels, particularly
in the lungs, cause cracks in heart valves and lead to hypertension.
The body has two ways of removing serotonin: by absorption into blood platelets that use it for clotting and through the erotonin-destroying enzyme monoamine oxidase, or MAO.
Some drugs block serotonin from being taken in by platelets; others block the activity of MAO. By using two of the drugs at the same time, the body's ability to keep serotonin in check is destroyed.
Phentermine is an MAO inhibitor, something researchers noted in the 1970s, but that fact was never added to the drug's warning label, MIT scientist Tim Maher said.
''To this day, if you ask 1,000 physicians or pharmacists if phentermine is an MAO inhibitor, they will say no. This information was buried. It never surfaced after the 1970s, and we're reconfirming it now,'' Maher said.
''Because this information is still omitted from the drug's label, many patients are now taking it with another serotonin-uptake blocker, Prozac, to lose weight,'' Maher said.
Other serotonin-uptake blockers such as pseudoephedrine, found in Sudafed, phenylpropanolamine, used in Acutrim, and ephedrine, a bronchial relaxant, may also be taken by people already using
phentermine, Maher's colleague Richard Wurtman said. The labels on those products clearly state they should not be taken if the patient is also using an MAO inhibitor.
''What good does it do to say, 'Never give with an MAO inhibitor,' if you don't know that an MAO inhibitor is in what you're prescribing?'' asked Wurtman, co-inventor of the anti-obesity drug Redux, the ''fen'' in fen-phen, which was withdrawn from the market in 1997. MIT holds the patent on
Redux, also known as dexfenfluramine.
American Home Products (AHP - news) is the target of dozens of class-action suits resulting from its manufacture of the diet drugs fenfluramine and dexfenfluramine, which were recalled last September. The company faces billions of dollars in potential liability after the FDA warned the two drugs might cause heart valve abnormalities.
Wurtman said if U.S. doctors had known phentermine was an MAO inhibitor, ''they never would have prescribed the drugs together.''
A spokesman for Eli Lilly (LLY - news), makers of Prozac, the decade's most popular antidepressant, said that in the 11 years the product had been available, ''there has been no such report of an adverse reaction.''
Last September, Lilly sent Nutri/System Weight-Loss Centers a kind of cease-and-desist letter when the Pennsylvania diet company launched an advertising campaign promoting the use of Prozac with phentermine.
''That was done not because we had any reports of adverse reactions but because we did not conduct safety tests for that use,'' Lilly spokesman Greg Keuterman said.
Dr. Judi Sills of Warner-Lambert (WLA - news), makers of Sudafed, said, ''We have 30 years of past data, and we have not had any reports of people who are on Sudafed and other products resulting in such an adverse reaction'' as hypertension or damage to heart valves.
FDA spokeswoman Ivy Kupec, while declining to comment on the specifics of phentermine, said the agency had the ability to update labeling information. ''We require new information on labels when we learn of adverse events through clinical trials or reports,'' she said.
Both Maher and Wurtman expect to meet with FDA officials after they present the results of their research at the International Congress of Obesity next week in Paris.
The pair's rediscovery of phentermine's MAO-inhibiting effects was serendipitous. Maher was researching the problems associated with fen-phen, while Wurtman wanted to see whether phentermine affected another chemical in the blood.
Maher quickly found the 1970s reports that phentermine was an MAO inhibitor, and Wurtman noted a spike in serotonin levels in volunteers for his experiment. They looked at the other drugs because Maher said they ''have similar chemical structures to fenfluramine.''
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